ESPE Abstracts

Introduction: Insulin resistance accelerates the onset of atherosclerosis and arterial stiffness in children. Trimethylamine N-oxide (TMAO), a gut-derived metabolite linked to cardio-metabolic issues in adults, could exacerbate these conditions in children as well. This study explores how insulin resistance and serum TMAO levels relate to vascular damage in obese children.

Methods: We included 60 children aged 6 to 18, divided into two groups: 35 obese children with insulin resistance (as determined by HOMA-IR, interpreted according to puberty stage) and 25 normal-weight children without insulin resistance. Assessments included BMI, waist circumference, waist-to-height ratio, puberty stage, and the presence of acanthosis nigricans. Arterial stiffness was evaluated through surrogate markers such as pulse wave velocity (PWV), augmentation index (AIx), and blood pressure measurements, using a Mobil-O-Graph single-point (brachial) oscillometer device. We also sonographically measured the carotid intima-media thickness (CIMT) to evaluate subclinical atherosclerosis, using the Aixplorer MACH 30 echography device. We further analyzed serum levels of TMAO, HOMA-IR, and other metabolic markers such as fasting glucose, uric acid, creatinine, lipid profile, triglycerides, transaminase, and 25-OH-Vitamin D.

Results: Obese children showed significantly higher TMAO levels compared to their normal-weight peers. TMAO was positively correlated with BMI, waist circumference, and waist-to-height ratio, and was an independent predictor of these measurements. It also correlated significantly with CIMT, PWV, and both peripheral and central blood pressure levels, maintaining its predictive ability even after adjusting for BMI, waist circumference, waist-to-height ratio, puberty development, and age. While HOMA-IR levels were closely linked to vascular markers, they did not correlate with TMAO levels. TMAO showed a negative correlation with fasting glucose levels. Subjects associating acanthosis nigricans had higher odds of presenting higher levels of TMAO (OR=1.2, P = 0.02).

Conclusion: This study underscores the association between TMAO, obesity, and vascular damage in children, independent of HOMA-IR. It is unclear whether HOMA-IR has higher limitations than expected in children even after adjusting for the puberty stage, as TMAO is more likely to be higher in children with acanthosis nigricans. The findings emphasize the complexity of metabolic interactions in obese children and highlight the need for further research on larger samples to decipher the mechanisms linking obesity and vascular damage in the pediatric population.